Human Endogenous Retroviruses

The aim of our research is to elucidate the functional role of Human Endogenous Retroviruses (HERVs) during stem cell differentiation and brain development using cutting-edge technologies including advanced CRISPR techniques in combination with human stem cell differentiation, the generation of brain organoids (mini brains in the dish) and bioinformatics analysis of large datasets.

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About our Research

Endogenous retroviruses (HERV) are a major component of the human genome. Constituting about 8 - 9% of the genomic DNA, they exceed by far the number of protein-coding gene sequences. Generally, they are extensively controlled and downregulated by genetic and epigenetic mechanisms. Activation by environmental factors such as chemicals, radiation and exogenous retroviruses, however, may lead to expression of undesired HERV gene products and dysregulation of cellular genes by HERV LTR sequences. The aim of our research is to elucidate the biological functions of HERVs, their involvement in evolutionary processes and their possible role in the development of disease.

Our present research focuses are

Deciphering the functional role of HERVs in stem cell differentiation and brain development
Expression and function of endogenous retroviruses in neuropathology
Activation of retroviral genes by environmental factors
Regulation of HERV regulatory sequences (LTRs)

Human Endogenous Retroviruses in Development

We develop new tools to study the functional role of HERVs during stem cell differentiation into neural cells. We directly manipulate specific HERV groups, using CRISPR technologies, in human stem cells followed by directed differentiation into neural subtypes and generation of brain organoids. In combination with large-scale gene expression analysis we elucidate the functional role and downstream effects of specific HERV groups on neural differentiation.

Human Endogenous Retroviruses in Neuropathology

The tight regulation of human endogenous retroviruses (HERVs) is essential for a healthy brain and dysregulation has been associated with neurodegenerative diseases. We are combining the differentiation of stem cells into different human brain cell types with CRISPR activation as well as CRISPR inhibition of specific HERV groups to systematically dissect how dysregulation of HERVs contributes to the development of neuropathology.

The X-ray of the human brain closeup image

Regulation of Human Endogenous Retroviruses

Several recent studies suggest that tight regulation of human endogenous retroviruses (HERVs) is essential during developmental processes, e.g. embryonal development, where activation of HERVs leads to regulation of tissue-specific genes. In human brain development, we could show that the exact timing of HERV-K(HML-2) expression is essential for proper cortical brain patterning as well as cortical neurogenesis. We use CRISPR-based approaches in combination with stem cell differetiations, to further understand the precise regulation of HERVs in different brain cell types.

Activation of Human Endogenous Retroviruses by Environmental Factors

Activation of human endogenous retroviruses (HERVs) can contribute to disease, including neurodegenrative diseases, through expression of HERV-derived viral proteins or dysregulation of cellular genes. Therefore, we are investigating the effects of various environmental factors (such as exogenous viruses) on HERV activation through transcriptional profiling to understand their impact on reactivation of HERVs and contribution to disease development.